Anthony W. Clare

Effect of Metyrapone on the Pituitary-Adrenal Axis in Depression Relation to Dexamethasone Suppressor Status

It has been suggested that the well-documented hypercortisolaemia found in a proportion of patients with severe depression occurs either in response to excessive secretion of corticotrophin-releasing hormone-41 (CRH-41) from the hypothalamus, or as a consequence of up-regulation of pituitary CRH-41 receptors. The attenuation of the normal ACTH response to CRH-41 in these subjects is thought to result from inhibition of corticotrophin secretion by elevated cortisol levels. We tested these hypotheses by examining ACTH responses to metyrapone, an 11 beta-hydroxylase inhibitor which blocks the formation of cortisol, followed by CRH-41 in 15 severely depressed in-patients diagnosed according to DSM-IIIR criteria. Patients were assigned to two groups according to their response to overnight administration of 1 mg dexamethasone: suppressors (8) and nonsuppressors (7). A third group consisted of 6 healthy matched controls. Metyrapone 750 mg was given 4-hourly for 24 h and samples were taken for cortisol and ACTH. Six of the original 15 patients (3 from each group) were given a bolus dose of 100 micrograms human CRH-41 intravenously after 24 h of metyrapone, and ACTH levels were measured over 2 h. Falls in circulating cortisol in response to metyrapone were similar in all three groups. However, we found exaggerated rises in ACTH amongst the nonsuppressors, as compared to the suppressors and the control group, after metyrapone.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet MAO activity in subtypes of alcoholics and controls in a homogenous population

The level of platelet monoamine oxidase (MAO) activity has been found to vary between alcoholics and healthy controls and between subtypes of alcoholics, in different populations. This study measured the MAO activity in a group of 46 abstinent alcohol dependent subjects and 22 healthy non-alcoholic controls, male and female, in an ethnically homogenous Irish population. The healthy control subjects had a mean MAO activity of 0.27 pmol/hr/10(5) platelets (+/- SEM 0.03), while the alcoholics overall had a mean activity of 0.34 pmol/hr/10(5) platelets (+/- 0.03) and this difference was not significant, P = 0.2. When the alcoholic group was divided into subtypes of alcoholism, (type 1 and type 2) there was no difference between subtypes of alcoholics nor between each subtype and the controls in their MAO activity. There was no correlation between MAO activity and the age of the subjects, the duration of abstinence from alcohol, the severity of alcoholism, smoking status or the gender of the subjects. These data are discussed in the context of the current literature on alcoholism and platelet MAO in different ethnic populations and the status of platelet MAO as a potential marker for alcoholism.

The anterior pituitary responds normally to protirelin in obsessive‐compulsive disorder: evidence to support a neuroendocrine serotonergic deficit

The prolactin and thyroid‐stimulating hormone (TSH) responses to protirelin and the prolactin and cortisol responses to d‐fenfluramine were measured in 8 outpatients with DSM‐III‐R obsessive‐compulsive disorder (OCD). The results were compared to those in 8 age‐ and sex‐matched healthy controls. The responses to d‐fenfluramine were significantly attenuated in the OCD patients, but there was no significant difference between the responses to protirelin in OCD patients and healthy controls. The data suggest that, in OCD, blunting of prolactin responses to the serotonin‐releasing agent d‐fenfluramine is due to a central abnormality and not due to a pituitary deficit.

Gender and age differences in the growth hormone response to pyridostigmine.

Thirty healthy subjects 12 males and 18 females were given the acetylcholinesterase inhibitor pyridostigmine (120 mg) orally. The growth hormone (GH) response was measured as the maximum GH level post-pyridostigmine relative to baseline. Twenty-six subjects increased their GH level in response to pyridostigmine. Responses in females were considerably greater than those in males and correlated closely with serum oestradiol levels. Overall there was a significant negative correlation between GH response and age.

Buspirone induced prolactin responses in obsessive-compulsive disorder (OCD): is OCD a 5-HT2 receptor disorder?

&NA; Buspirone (BUSP) is a serotonergic (5‐HT) agonist with activity at the 5‐HT1A receptor. The BUSP induced prolactin (PRL) response was examined in 10 patients with a DSM IIIR diagnosis of obsessive‐compulsive disorder (OCD). The results were compared with PRL responses to BUSP found in 10 age and sex matched healthy controls. The results suggest that the 5‐HT1A receptor dysfunction may not be involved in the pathophysiology of OCD. The authors review the literature and consider the hypothesis that in OCD a complex interaction of other 5‐HT receptor sub‐types may be occurring, possibly with dysfunction primarily of the 5‐HT2 receptors.

Psychiatric aspects of abortion

Objective: To examine the evidence concerning the psychological consequences of abortion, the risk of suicide in pregnancy and the psychological consequences for the mother and the child in cases of refused abortion. Method: An extensive literature search was undertaken and key relevant papers were examined and analysed. Results: Legal abortion has become more widely available throughout the western world and the actual reported incidence of cases of refused abortion is low. The majority of studies indicate that the psychological consequences of abortion itself are in the main mild and transient but there is evidence that women who have strong religious or cultural attitudes negative to abortion do experience high levels of psychological stress following abortion. The risk of suicide is low in pregnancy and suicide is a rare outcome of refused abortion. There is evidence of psychological and social difficulties experienced by mothers of unwanted pregnancies forced to proceed to term and by many offspring of such unwanted pregnancies. Conclusions: Definitive conclusions are difficult to draw from the published studies of refused abortion and many studies are over thirty years old.

Serum thyrotropin responses to thyrotropin-releasing hormone in alcohol-dependent patients with and without depression

Forty-one patients with DSM-III alcohol dependence syndrome were studied, as were 30 patients with major depression and 20 healthy controls. Nineteen of the alcohol-dependent patients had depressive symptoms. All subjects underwent a TRH/TSH stimulation test. Fifty percent of the alcohol-dependent patients without depression had a blunted response, while 52% of patients with depression were similarly blunted. The overall rate of blunting in the non-alcoholic major depressives was 26%. Blunting in the alcoholics was not associated with a personal or family history of affective disorder. Furthermore the blunted response in recently detoxified alcoholics was of no prognostic significance.

The clinical characteristics of patients with obsessive compulsive disorder: a descriptive study of an Irish sample

Objective: To describe the clinical characteristics and demographic details of a sample of patients with a principal diagnosis of obsessive compulsive disorder (OCD). Method: A retrospective review of fifty patients with DSM-III-R OCD referred to the Department of Behaviour Therapy at St. Patricks Hospital, Dublin, Ireland between 1990 and 1991. Standard clinical ratings were made before and after treatment. Ratings used included the Maudsley Obsessive Compulsive Inventory (MOCI), the Fear Questionnaire (FQ), and the Yale-Brown obsessive compulsive score (YBOCS). Results: The male to female ratio was almost equal and the mean duration of illness was 6.1 (SD 11 years). OCD presented in isolation in a minority of cases (14%). A life time history of at least one other DSM-III-R axis I diagnosis, especially depression, was found in 72% of patients. Co-morbid Gilles de la Tourettes syndrome or epilepsy was rare. The majority of patients were on medication prior to presentation (78%). Levels of symptomatology were reduced in 91% of patients who completed treatment. Conclusions: Epidemiological research into the mass aspects of this disorder is required.

Personality disorder among first ever admissions to an Irish public and private hospital

Objective: The identification of personality disorder among psychiatric in-patients is important because of the effect on the course and outcome of illness. The introduction of a multiaxial approach to diagnosis, has resulted in a higher than previously reported rate of occurrence of personality disorder in a variety of psychiatric settings. A prevalence of personality disorder of 4.9% is reported in the official statistics for Irish psychiatric hospitals. The aim of this study is to determine the true prevalence of personality disorders in two Irish psychiatric hospitals, one public and one private, using a multiaxial approach to diagnosis. Methods: The Standardised Assessment of Personality (SAP) is a validated, semistructured, informant based instrument that reliably generates diagnoses of personality disorder irrespective of current mental state. Over a four month period, 78 consecutive, first ever admissions to two hospitals were examined using the SAP. Results: The prevalence of personality disorder in this population was 26%. There was no significant difference in the rate of personality disorder between the public and private institutions. Conclusions: The prevalence of personality disorder amongst in-patients in both public and private psychiatric hospitals in Ireland is far higher than previously reported. This highlights the importance of a multiaxial approach to diagnosis in order to establish the true extent of psychiatric morbidity.